Meta-analysis of genome-wide association studies of aggressive and chronic periodontitis identifies two novel risk loci

Matthias Munz; Gesa M. Richter; Bruno G. Loos; Søren Jepsen; Kimon Divaris; Steven Offenbacher; Alexander Teumer; Birte Holtfreter; Thomas Kocher; Corinna Bruckmann; Yvonne Jockel-Schneider; Christian Graetz; Ilyas Ahmad; Ingmar Staufenbiel; Nathalie van der Velde; André G. Uitterlinden; Lisette C.P.G.M. de Groot; Jürgen Wellmann; Klaus Berger; Bastian Krone; Per Hoffmann; Matthias Laudes; Wolfgang Lieb; Andre Franke; Jeanette Erdmann; Henrik Dommisch; Arne S. Schaefer

doi:10.1038/s41431-018-0265-5

Meta-analysis of genome-wide association studies of aggressive and chronic periodontitis identifies two novel risk loci

Matthias Munz, Gesa M. Richter, Bruno G. Loos, Søren Jepsen, Kimon Divaris, Steven Offenbacher, Alexander Teumer, Birte Holtfreter, Thomas Kocher, Corinna Bruckmann, Yvonne Jockel-Schneider, Christian Graetz, Ilyas Ahmad, Ingmar Staufenbiel, Nathalie van der Velde, André G. Uitterlinden, Lisette C.P.G.M. de Groot, Jürgen Wellmann, Klaus Berger, Bastian KronePer Hoffmann, Matthias Laudes, Wolfgang Lieb, Andre Franke, Jeanette Erdmann, Henrik Dommisch, Arne S. Schaefer^*

^*Corresponding author for this work

70 Citations (Scopus)

Abstract

Periodontitis is one of the most common inflammatory diseases, with a prevalence of 11% worldwide for the severe forms and an estimated heritability of 50%. It is classified into the widespread moderate form chronic periodontitis (CP) and the rare early-onset and severe phenotype aggressive periodontitis (AgP). These different disease manifestations are thought to share risk alleles and predisposing environmental factors. To obtain novel insights into the shared genetic etiology and the underlying molecular mechanisms of both forms, we performed a two step-wise meta-analysis approach using genome-wide association studies of both phenotypes. Genotypes from imputed genome-wide association studies (GWAS) of AgP and CP comprising 5,095 cases and 9,908 controls of North-West European genetic background were included. Two loci were associated with periodontitis at a genome-wide significance level. They located within the pseudogene MTND1P5 on chromosome 8 (rs16870060-G, P = 3.69 × 10 ⁻⁹ , OR = 1.36, 95% CI = [1.23–1.51]) and intronic of the long intergenic non-coding RNA LOC107984137 on chromosome 16, downstream of the gene SHISA9 (rs729876-T, P = 9.77 × 10 ⁻⁹ , OR = 1.24, 95% CI = [1.15–1.34]). This study identified novel risk loci of periodontitis, adding to the genetic basis of AgP and CP.

Original language	English
Journal	European Journal of Human Genetics
Volume	27
Issue number	1
Pages (from-to)	102-113
Number of pages	12
ISSN	1018-4813
DOIs	https://doi.org/10.1038/s41431-018-0265-5
Publication status	Published - 01.01.2019

Funding

Acknowledgements This work was supported by a research grant of the German Research Foundation DFG (Deutsche For-schungsgemeinschaft; GZ: SCHA 1582/3-1). Collection of the AgP cases was additionally supported by the German Ministry of Education and Research through the POPGEN biobank project (01GR0468). The Dortmund Health Study (DHS) is supported by the German Migraine & Headache Society (DMKG) and by unrestricted grants of equal share from Almirall, Astra Zeneca, Berlin Chemie, Boehringer, Boots Health Care, Glaxo-Smith-Kline, Janssen Cilag, McNeil Pharma, MSD Sharp and Dohme and Pfizer to the University of Muenster (collection of sociodemographic and clinical data). Blood collection in the Dortmund Health Study was done through funds from the Institute of Epidemiology and Social Medicine University of Muenster and genotyping supported by the German Ministry of Research and Education (BMBF, grant no. 01ER0816). FOCUS was supported by the Federal Ministry of Education and Research BMBF (FKZ 0315540 A). The HNR study is supported by the Heinz Nixdorf Foundation (Germany). Additionally, the HNR study was funded by the German Ministry of Education and Science and the German Research Council (DFG; Project SI 236/8-1, SI236/9-1, ER 155/6-1). The genotyping of the Illumina HumanOmni-1 Quad BeadChips of the HNR subjects was financed by the German Centre for Neurodegenerative Diseases (DZNE), Bonn. SHIP is part of the Community Medicine Research net (http://www.community-medicine.de) of the University of Greifs-wald, Germany, which is funded by the Federal Ministry of Education and Research (grants no. 01ZZ9603, 01ZZ0103, and 01ZZ0403), the Ministry of Cultural Affairs, as well as the Social Ministry of the Federal State of Mecklenburg-West Pomerania. Generation of genome-wide SNP data has been supported by the Federal Ministry of Education and Research (grant no. 03ZIK012) and a joint grant from Siemens Healthcare, Erlangen, Germany and the Federal State of Mecklenburg, West Pomerania. The University of Greifswald is a member of the Caché Campus program of the InterSystems GmbH.

Research Areas and Centers

Research Area: Medical Genetics

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1038/s41431-018-0265-5

Cite this

Munz, M., Richter, G. M., Loos, B. G., Jepsen, S., Divaris, K., Offenbacher, S., Teumer, A., Holtfreter, B., Kocher, T., Bruckmann, C., Jockel-Schneider, Y., Graetz, C., Ahmad, I., Staufenbiel, I., van der Velde, N., Uitterlinden, A. G., de Groot, L. C. P. G. M., Wellmann, J., Berger, K., ... Schaefer, A. S. (2019). Meta-analysis of genome-wide association studies of aggressive and chronic periodontitis identifies two novel risk loci. European Journal of Human Genetics, 27(1), 102-113. https://doi.org/10.1038/s41431-018-0265-5

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title = "Meta-analysis of genome-wide association studies of aggressive and chronic periodontitis identifies two novel risk loci",

abstract = " Periodontitis is one of the most common inflammatory diseases, with a prevalence of 11\% worldwide for the severe forms and an estimated heritability of 50\%. It is classified into the widespread moderate form chronic periodontitis (CP) and the rare early-onset and severe phenotype aggressive periodontitis (AgP). These different disease manifestations are thought to share risk alleles and predisposing environmental factors. To obtain novel insights into the shared genetic etiology and the underlying molecular mechanisms of both forms, we performed a two step-wise meta-analysis approach using genome-wide association studies of both phenotypes. Genotypes from imputed genome-wide association studies (GWAS) of AgP and CP comprising 5,095 cases and 9,908 controls of North-West European genetic background were included. Two loci were associated with periodontitis at a genome-wide significance level. They located within the pseudogene MTND1P5 on chromosome 8 (rs16870060-G, P = 3.69 × 10 −9 , OR = 1.36, 95\% CI = [1.23–1.51]) and intronic of the long intergenic non-coding RNA LOC107984137 on chromosome 16, downstream of the gene SHISA9 (rs729876-T, P = 9.77 × 10 −9 , OR = 1.24, 95\% CI = [1.15–1.34]). This study identified novel risk loci of periodontitis, adding to the genetic basis of AgP and CP. ",

author = "Matthias Munz and Richter, \{Gesa M.\} and Loos, \{Bruno G.\} and S{\o}ren Jepsen and Kimon Divaris and Steven Offenbacher and Alexander Teumer and Birte Holtfreter and Thomas Kocher and Corinna Bruckmann and Yvonne Jockel-Schneider and Christian Graetz and Ilyas Ahmad and Ingmar Staufenbiel and \{van der Velde\}, Nathalie and Uitterlinden, \{Andr{\'e} G.\} and \{de Groot\}, \{Lisette C.P.G.M.\} and J{\"u}rgen Wellmann and Klaus Berger and Bastian Krone and Per Hoffmann and Matthias Laudes and Wolfgang Lieb and Andre Franke and Jeanette Erdmann and Henrik Dommisch and Schaefer, \{Arne S.\}",

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Munz, M, Richter, GM, Loos, BG, Jepsen, S, Divaris, K, Offenbacher, S, Teumer, A, Holtfreter, B, Kocher, T, Bruckmann, C, Jockel-Schneider, Y, Graetz, C, Ahmad, I, Staufenbiel, I, van der Velde, N, Uitterlinden, AG, de Groot, LCPGM, Wellmann, J, Berger, K, Krone, B, Hoffmann, P, Laudes, M, Lieb, W, Franke, A, Erdmann, J, Dommisch, H & Schaefer, AS 2019, 'Meta-analysis of genome-wide association studies of aggressive and chronic periodontitis identifies two novel risk loci', European Journal of Human Genetics, vol. 27, no. 1, pp. 102-113. https://doi.org/10.1038/s41431-018-0265-5

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T1 - Meta-analysis of genome-wide association studies of aggressive and chronic periodontitis identifies two novel risk loci

AU - Munz, Matthias

AU - Richter, Gesa M.

AU - Loos, Bruno G.

AU - Jepsen, Søren

AU - Divaris, Kimon

AU - Offenbacher, Steven

AU - Teumer, Alexander

AU - Holtfreter, Birte

AU - Kocher, Thomas

AU - Bruckmann, Corinna

AU - Jockel-Schneider, Yvonne

AU - Graetz, Christian

AU - Ahmad, Ilyas

AU - Staufenbiel, Ingmar

AU - van der Velde, Nathalie

AU - Uitterlinden, André G.

AU - de Groot, Lisette C.P.G.M.

AU - Wellmann, Jürgen

AU - Berger, Klaus

AU - Krone, Bastian

AU - Hoffmann, Per

AU - Laudes, Matthias

AU - Lieb, Wolfgang

AU - Franke, Andre

AU - Erdmann, Jeanette

AU - Dommisch, Henrik

AU - Schaefer, Arne S.

PY - 2019/1/1

Y1 - 2019/1/1

N2 - Periodontitis is one of the most common inflammatory diseases, with a prevalence of 11% worldwide for the severe forms and an estimated heritability of 50%. It is classified into the widespread moderate form chronic periodontitis (CP) and the rare early-onset and severe phenotype aggressive periodontitis (AgP). These different disease manifestations are thought to share risk alleles and predisposing environmental factors. To obtain novel insights into the shared genetic etiology and the underlying molecular mechanisms of both forms, we performed a two step-wise meta-analysis approach using genome-wide association studies of both phenotypes. Genotypes from imputed genome-wide association studies (GWAS) of AgP and CP comprising 5,095 cases and 9,908 controls of North-West European genetic background were included. Two loci were associated with periodontitis at a genome-wide significance level. They located within the pseudogene MTND1P5 on chromosome 8 (rs16870060-G, P = 3.69 × 10 −9 , OR = 1.36, 95% CI = [1.23–1.51]) and intronic of the long intergenic non-coding RNA LOC107984137 on chromosome 16, downstream of the gene SHISA9 (rs729876-T, P = 9.77 × 10 −9 , OR = 1.24, 95% CI = [1.15–1.34]). This study identified novel risk loci of periodontitis, adding to the genetic basis of AgP and CP.

AB - Periodontitis is one of the most common inflammatory diseases, with a prevalence of 11% worldwide for the severe forms and an estimated heritability of 50%. It is classified into the widespread moderate form chronic periodontitis (CP) and the rare early-onset and severe phenotype aggressive periodontitis (AgP). These different disease manifestations are thought to share risk alleles and predisposing environmental factors. To obtain novel insights into the shared genetic etiology and the underlying molecular mechanisms of both forms, we performed a two step-wise meta-analysis approach using genome-wide association studies of both phenotypes. Genotypes from imputed genome-wide association studies (GWAS) of AgP and CP comprising 5,095 cases and 9,908 controls of North-West European genetic background were included. Two loci were associated with periodontitis at a genome-wide significance level. They located within the pseudogene MTND1P5 on chromosome 8 (rs16870060-G, P = 3.69 × 10 −9 , OR = 1.36, 95% CI = [1.23–1.51]) and intronic of the long intergenic non-coding RNA LOC107984137 on chromosome 16, downstream of the gene SHISA9 (rs729876-T, P = 9.77 × 10 −9 , OR = 1.24, 95% CI = [1.15–1.34]). This study identified novel risk loci of periodontitis, adding to the genetic basis of AgP and CP.

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Meta-analysis of genome-wide association studies of aggressive and chronic periodontitis identifies two novel risk loci

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Genome-wide Association Study for the Identification of Genetic Risk Factors of Periodontitis

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Meta-analysis of genome-wide association studies of aggressive and chronic periodontitis identifies two novel risk loci

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Genome-wide Association Study for the Identification of Genetic Risk Factors of Periodontitis

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